For ADHD, we have carried out a case-control study in a local school district. We are currently preparing a manuscript on ADHD prevalence among elementary school children. Based on our epidemiologic case definition, 15.5% of children in grades 1-5 in this school district had ADHD. Though higher than many estimates, ours is based on systematic screening of all children in the schools and so captures children who may not be evaluated in studies involving clinical diagnoses. Future work will address environmental lead exposure as a possible risk factor for ADHD. (see Z01 ES49034;PI Dale Sandler, EB) For ALS, based on a case-control study that we conducted several years ago, we completed two manuscripts examining risk factors for ALS: one on occupational exposures and one on polymorphisms in the DNA repair gene XRCC1. We found that construction workers and precision metal worker were at higher risk of ALS and that self-reported exposure to paint strippers, lubricating oils, mineral spirits, and dry cleaning agents also appeared to elevate risk. Our examination of 5 SNP loci in XRCC1 suggested that, for 2 of them, carriers of the variant allele had slightly lower risk of ALS. We are undertaking a study of the relationship between blood lead levels, biomarkers of bone turnover (indicators of mobilization of lead sequestered in bone), and risk of ALS using the Veterans Administration ALS cohort. (see Z01 ES49005;LI Freya Kamel, EB) We have carried out a case-control study nested within the Agricultural Health Study to examine associations between Parkinson's disease and environmental risk factors, particularly certain pesticide exposures. We are also looking at selected candidate genes as susceptibility factors. This study employs data from the Agricultural Health Study as well as additional questionnaire data and field samples collected expressly for this effort. Analysis of data is underway. Several reports have been presented at national meetings including separate investigations of metal levels in blood, alpha-synuclein gene variants, and OCT2 gene variants as risk or susceptibility factors for Parkinson's disease;the corresponding manuscripts are in preparation. (see Z01 ES44007 EB;LI Freya Kamel, EB) Analysis of data from the pilot study of the effects of soy estrogen on neonatal development is nearly complete. We published a finding that salivary cortisol levels are about 40% higher in breast-fed infants than formula-fed infants, contradicting our hypothesis that breast-fed infants would have lower levels this stress hormone because breast-feeding provides more maternal contact, hence less stress, than bottle feeding. A manuscript is in preparation reporting on developmental trajectories through infancy in the size of several putatively estrogen-sensitive organs based on ultrasound imaging. The full-scale study is currently being developed using results from the pilot, and we expect to begin collecting data next spring or summer. (see Z01 ES44006 EB;PI Walter Rogan, EB)